The WT1 gene (Wilms' tumor 1 gene) is a gene identified as a causative gene of a Wilms' tumor which is a kidney cancer in childhood (Non-Patent Documents 1 and 2), and is a transcription factor having a zinc finger structure. At first, the WT1 gene was considered to be a cancer suppressor gene. However, subsequent investigation showed that the above gene rather serves as a cancer gene in hematopoietic organ tumors and solid cancers (Non-Patent Documents 3 to 6).
Since the WT1 gene is highly expressed in many malignant tumors, a WT1 gene product which is a self-protein having no mutation has been verified for existence or non-existence of immunogenicity in vivo. As a result, it has been shown that a protein derived from the WT1 gene highly expressed in tumor cells is fragmented by intracellular processing and the resulting peptide forms a complex with an MHC class I molecule which is displayed on the cell surface, and that cytotoxic T cells (hereinafter also referred to as CTLs) recognizing such a complex can be induced by WT1 peptide vaccination (Non-Patent Documents 7 to 9). It has also been shown that mice immunized with a WT1 peptide or a WT1 cDNA reject implanted WT1 gene-expressing tumor cells in a high rate (Non-Patent Documents 7 and 10) but normal tissues endogenously expressing the WT1 gene are not damaged by induced CTLs (Non-Patent Document 7). Heretofore, it has been strongly suggested that it is possible to induce WT1-specific CTLs in not only mice but also human, and that such CTLs have a cytotoxic activity against tumor cells highly expressing the WT1 gene, but have no cytotoxic activity against normal cells endogenously expressing the WT1 gene (Non-Patent Documents 7 and 10 to 14).
On the other hand, it is reported that the presence of helper T cells specific to a cancer antigen is important in order to induce the CTLs effectively (Non-Patent Document 15). The helper T cells (CD4-positive T cells) are induced, proliferated, and activated by recognizing a complex of an MHC class II molecule with an antigen peptide on antigen presenting cells. Activated helper T cells produce cytokines such as IL-2, IL-4, IL-5, IL-6, or an interferon (IFN), and promote proliferation, differentiation and maturation of B cells and other subsets of T cells. Thus, it is considered that an antigen peptide binding to an MHC class II molecule effectively activates CTLs and others through induction of helper T cells and enhances an immune function (Non-Patent Document 16). Heretofore, only an antigen peptide binding to HLA-DRB1*0401 and HLA-DRB1*0405 of an MHC class II molecule has been reported with respect to WT1 (Non-Patent Document 17 and Patent Document 1), and it was necessary to find antigen peptides to other subtypes.